Limits...
Simvastatin may induce insulin resistance through a novel fatty acid mediated cholesterol independent mechanism.

Kain V, Kapadia B, Misra P, Saxena U - Sci Rep (2015)

Bottom Line: Statins are a class of oral drugs that are widely used for treatment of hypercholesterolemia.We explored the possible mechanism of statin induced insulin resistance using a well-established cell based model and simvastatin as a prototype statin.Our data show that simvastatin induces insulin resistance in a cholesterol biosynthesis inhibition independent fashion but does so by a fatty acid mediated effect on insulin signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.

ABSTRACT
Statins are a class of oral drugs that are widely used for treatment of hypercholesterolemia. Recent clinical data suggest that chronic use of these drugs increases the frequency of new onset diabetes. Studies to define the risks of statin-induced diabetes and its underlying mechanisms are clearly necessary. We explored the possible mechanism of statin induced insulin resistance using a well-established cell based model and simvastatin as a prototype statin. Our data show that simvastatin induces insulin resistance in a cholesterol biosynthesis inhibition independent fashion but does so by a fatty acid mediated effect on insulin signaling pathway. These data may help design strategies for prevention of statin induced insulin resistance and diabetes in patients with hypercholesterolemia.

No MeSH data available.


Related in: MedlinePlus

Simvastatin and Atorvastatin block insulin mediated glucose uptake: Mean basal and insulin stimulated (5 min and 10 min) uptake of 2-NBDG by L6 myotubes treated with Simvastatin (1 μM) (a) and Atorvastatin (b) for different time points as indicated. DMSO (0.1%) treated cells served as internal control. Values are shown as mean±SD after normalizing with the corresponding protein content and expressed relative to basal of control cells which was set to 1; *p < 0.05 ,**p < 0.01, versus corresponding control cells (two way ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4561915&req=5

f1: Simvastatin and Atorvastatin block insulin mediated glucose uptake: Mean basal and insulin stimulated (5 min and 10 min) uptake of 2-NBDG by L6 myotubes treated with Simvastatin (1 μM) (a) and Atorvastatin (b) for different time points as indicated. DMSO (0.1%) treated cells served as internal control. Values are shown as mean±SD after normalizing with the corresponding protein content and expressed relative to basal of control cells which was set to 1; *p < 0.05 ,**p < 0.01, versus corresponding control cells (two way ANOVA).

Mentions: To explore if simvastatin could induce insulin resistance like phenotype in an in vitro model, we explored its effects on the uptake of glucose using a L6 myotubes model (Supplemental Fig. 1). The effect of simvastatin on glucose uptake was observed in myotubes with and without treatment with insulin using 2-NBDG as a marker for glucose uptake. Addition of simvastatin to control cells (no treatment with insulin) had minimal effect on glucose uptake (Supplemental Fig. 1). However addition of simvastatin followed by insulin stimulation, markedly inhibited glucose uptake (~5% after 4 h, ~8% after 12 h, ~40% after 24 h and ~60% after 48 h of treatment compared to DMSO treated control cells post 5minutes of stimulation with insulin) (Fig. 1a). We also examined the effects of atorvastatin, another statin that is clinically used but its chemical structure is distinct from that of simvastatin. As shown in Fig. 1b, atorvastatin treatment also reduced insulin stimulated glucose uptake. These data show that two distinct statins, simvastatin and atorvastatin can inhibit insulin-mediated uptake of glucose. Prolonged simvastatin treatment (48 h) showed marginal decrease in glucose uptake of control cells, while atorvastatin displayed modest increase in glucose uptake of control cells (statistically non significant). Collectively these data show that these two statins impair insulin-mediated but not non-insulin mediated glucose uptake.


Simvastatin may induce insulin resistance through a novel fatty acid mediated cholesterol independent mechanism.

Kain V, Kapadia B, Misra P, Saxena U - Sci Rep (2015)

Simvastatin and Atorvastatin block insulin mediated glucose uptake: Mean basal and insulin stimulated (5 min and 10 min) uptake of 2-NBDG by L6 myotubes treated with Simvastatin (1 μM) (a) and Atorvastatin (b) for different time points as indicated. DMSO (0.1%) treated cells served as internal control. Values are shown as mean±SD after normalizing with the corresponding protein content and expressed relative to basal of control cells which was set to 1; *p < 0.05 ,**p < 0.01, versus corresponding control cells (two way ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561915&req=5

f1: Simvastatin and Atorvastatin block insulin mediated glucose uptake: Mean basal and insulin stimulated (5 min and 10 min) uptake of 2-NBDG by L6 myotubes treated with Simvastatin (1 μM) (a) and Atorvastatin (b) for different time points as indicated. DMSO (0.1%) treated cells served as internal control. Values are shown as mean±SD after normalizing with the corresponding protein content and expressed relative to basal of control cells which was set to 1; *p < 0.05 ,**p < 0.01, versus corresponding control cells (two way ANOVA).
Mentions: To explore if simvastatin could induce insulin resistance like phenotype in an in vitro model, we explored its effects on the uptake of glucose using a L6 myotubes model (Supplemental Fig. 1). The effect of simvastatin on glucose uptake was observed in myotubes with and without treatment with insulin using 2-NBDG as a marker for glucose uptake. Addition of simvastatin to control cells (no treatment with insulin) had minimal effect on glucose uptake (Supplemental Fig. 1). However addition of simvastatin followed by insulin stimulation, markedly inhibited glucose uptake (~5% after 4 h, ~8% after 12 h, ~40% after 24 h and ~60% after 48 h of treatment compared to DMSO treated control cells post 5minutes of stimulation with insulin) (Fig. 1a). We also examined the effects of atorvastatin, another statin that is clinically used but its chemical structure is distinct from that of simvastatin. As shown in Fig. 1b, atorvastatin treatment also reduced insulin stimulated glucose uptake. These data show that two distinct statins, simvastatin and atorvastatin can inhibit insulin-mediated uptake of glucose. Prolonged simvastatin treatment (48 h) showed marginal decrease in glucose uptake of control cells, while atorvastatin displayed modest increase in glucose uptake of control cells (statistically non significant). Collectively these data show that these two statins impair insulin-mediated but not non-insulin mediated glucose uptake.

Bottom Line: Statins are a class of oral drugs that are widely used for treatment of hypercholesterolemia.We explored the possible mechanism of statin induced insulin resistance using a well-established cell based model and simvastatin as a prototype statin.Our data show that simvastatin induces insulin resistance in a cholesterol biosynthesis inhibition independent fashion but does so by a fatty acid mediated effect on insulin signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, Telangana, India.

ABSTRACT
Statins are a class of oral drugs that are widely used for treatment of hypercholesterolemia. Recent clinical data suggest that chronic use of these drugs increases the frequency of new onset diabetes. Studies to define the risks of statin-induced diabetes and its underlying mechanisms are clearly necessary. We explored the possible mechanism of statin induced insulin resistance using a well-established cell based model and simvastatin as a prototype statin. Our data show that simvastatin induces insulin resistance in a cholesterol biosynthesis inhibition independent fashion but does so by a fatty acid mediated effect on insulin signaling pathway. These data may help design strategies for prevention of statin induced insulin resistance and diabetes in patients with hypercholesterolemia.

No MeSH data available.


Related in: MedlinePlus